13 April 2025 : Review article
Inclisiran in Cardiovascular Health: A Review of Mechanisms, Efficacy, and Future Prospects
Fanke Huang ABCDEFG 1, Qiuting Dai FG 1, Yilu Zhou F 1, Jing Guan F 1, Jingjing Wu F 1, Yanyan Dong F 1, Jianfeng Lv AG 1*DOI: 10.12659/MSM.946439
Med Sci Monit 2025; 31:e946439
Table 2 Features and results of clinical trials of inclisiran in the treatment of hyperlipidemia.
| Study name | Study object | Study group | Study design | Study target | Primary outcome measures | Research time | Study status |
|---|---|---|---|---|---|---|---|
| ORION-3 | High-risk ASCVD patients with elevated LDL-C | The research was extended on the basis of the ORION-1 study group | An open-label, multicenter, non-randomized, actively compared, long-term extended Phase II trial | To compare the effects of long-term subcutaneous injections of inclisiran and Evolocumab in subjects at high cardiovascular risk with elevated LDL-C | Percentage change in LDL-C levels from baseline in the Oriorion-1 study to day 210 of the Oriorion-3 study | 2017-04-27 to 2021-12-17 | Completed |
| ORION-15 | HeFH, CAD, JAS2017 guidelines classify Japanese patients with elevated LDL-C levels as “high risk | Participants were ranomized 1: 1 | A randomized, double-blind, placebo-controlled trial | To evaluate the effects of subcutaneous injections of different doses of inclisiran in Japanese subjects | To evaluate the effects of subcutaneous injections of different doses of inclisiran in Japanese subjects | 2021-01-29 to 2022-10-19 | Completed |
| ORION-7 | Patients with ASCVD with elevated LDL-C | The subjects were divided into normal, mild, moderate and severe renal function impairment groups according to the degree of renal function impairment | A single-dose, open-label phase I clinical trial | To compare the pharmacokinetics, pharmacodynamics, safety, and tolerability of inclisiran in subjects with normal renal function vs those with impaired renal function | Pharmacokinetic indices at 0, 0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h after administration and at day 4, day 7, day 14 and day 30 after administration | 2017-06-22 to 2018-03-24 | Completed |
| ORION-5 | HoFH patients | Participants were randomized 1: 1 | A two-part (double-blind placebo-controlled/open-label), multicenter phase III trial | To evaluate the safety, tolerability, and efficacy of inclisiran in HoFH subjects | Percentage change in LDL-C levels from baseline to day 150 | 2019-02-06 to 2021-09-09 | Completed |
| ORION-13 | Adolescent patients with HeFH | Participants were randomized 1: 1 | A 2-part (1-year double-blind and 1-year open-label) multicenter trial | To evaluate the safety, tolerability, and efficacy of inclisiran in homozygous adolescents with familial hypercholesterolemia | Percentage change in LDL-C levels from baseline to 330 days | 2021-02-16 to 2024-12-02 | Underway |
| ORION-8 | Patients with elevated LDL-C ASCVD, ASCVD risk equivalence, and HeFH | The research was expanded on the basis of the ORION-3, ORION-9, ORION-10, and ORION-11 study groups | A long-term scaling trial of open labels | To evaluate the long-term efficacy, safety and tolerability of inclisiran | The proportion of subjects with satisfactory lipid control from day 1 of ORION-8 to the end of the study; Incidence of adverse events (TEAE) from day 1 of ORION-8 to the end of the study | 2019-04-16 to 2023-02-13 | Completed |
| ORION-1 | Patients with ASCVD with elevated LDL-C and ASCVD risk equivalence | Participants were randomized into 6 groups | A randomized, double-blind, placebo-controlled phase II trial | To compare the effects of single or multiple subcutaneous injections of different doses of inclisiran on ASCVD and ASCVD risk equivalent subjects with elevated LDL-C | Percentage change in LDL-C levels from baseline to day 180 | 2018-10-30 to 2026-07-30 | Underway |
| ORION-9 | Patients with HeFH | articipants were arandoamized 1: 1 | A randomized, double-blind, placebo-controlled phase III trial | To evaluate the efficacy, safety, and tolerability aof subcutaneous injections of inclisiran | Percentage change in LDL-C levels froam baseline to day 5aa10 | 2017-11-28 to 2019-09-17 | Completed |
| Study name | Study object | Study group | Study design | Study target | Primary outcome measures | Research time | Study status |
| ORION-11 | Patients with ASCVD with elevated LDL-C and ASCVD risk equivalence | Participants were randomized 1: 1 | A randomized, double-blind, placebo-controlled, phase III trial | To evaluate the efficacy, safety, and tolerability of subcutaneous injections of inclisiran | Percentage change in LDL-C levels from baseline to day 510 | 2017-11-01 to 2019-08-27 | Completed |
| LIBerate-VI | In patients with very high or high-risk CVD | Participants were randomized 1: 1 | A randomized, open-label (lipid-blind), phase III trial | To compare the efficacy and safety of Lerodalcibep with inclisiran in patients with very high or high-risk CVD | Percentage change in LDL-C levels from baseline to day 270 | 2022-06-20 to 2024-07-30 | Underway |
| V-Mono China | Low-moderate-risk ASCVD patients with elevated LDL-C in China | Patients with low or moderate ASCVD risk, fasting LDL-C values ≥130 mg/dL <190 mg/dL, and not receiving any lipid-lowering therapy were 1: 1 randomized | A randomized, double-blind, multicenter phase III trial | To evaluate the efficacy and safety of inclisiran as a monotherapy for Chinese adults at low or moderate risk of ASCVD with elevated LDL-C | Percentage change in LDL-C levels from baseline to 150 days | 2023-07-11 to 2024-10-28 | Underway |
| Study name | Study object | Study group | Study design | Study target | Primary outcome measures | Research time | Study status |
| ORION-14 | Patients receiving maximum doses of lipid-lowering drugs who still have poor control of LDL-C levels | Random allocation | A randomized, blind (participant, investigator, and sponsor), placebo-controlled trial | To evaluate the pharmacokinetics and pharmacodynamics of single dose subcutaneous injection of inclisiran | Percentage change in LDL-C and PCSK9 levels from baseline to days 5, 8, 15, 30, 60, and 90; Pharmacokinetic parameters of inclisiran within 48 h after administration | 2021-02-26 to 2021-10-18 | Completed |
| VICTORION-INITIATEE | Patients with ASCVD with elevated LDL-C | 444 participants were randomized 1: 1 | A randomized, two-arm, parallel group, open-label, multicenter clinical trial | To evaluate the pharmacodynamics of inclisiran vs conventional lipid-lowering therapy | Percentage change in LDL-C levels from baseline to 330 days | 2021-06-25 to 2023-09-15 | Completed |
| ORION-2 | HoFH patients | Single group allocation | An open-label, single-arm, multicenter trial | To evaluate the safety, tolerability, and efficacy of inclisiran in HoFH participants | Percentage change in LDL-C levels from baseline to day 180 | 2021-01-29 to 2022-10-19 | Completed |
| V-PEDS-OLE | Adolescent patients with HeFH or HoFH | Extensibility studies have been completed for patients in the ORION-16 and ORION-13 studies | A randomized, double-blind, multicenter phase III trial | To evaluate the efficacy and safety of inclisiran as a monotherapy for Chinese adults at low or moderate risk of ASCVD with elevated LDL-C | Percentage change in LDL-C levels from baseline to 150 days | 2023-07-11 to 2024-10-28 | Underway |
| Study name | Study object | Study group | Study design | Study target | Primary outcome measures | Research time | Study status |
| VICTORION-2P | Patients with confirmed cardiovascular disease (CVD) | Participants were randomized 1: 1 | A randomized, double-blind, placebo-controlled, multicenter trial | To evaluate the benefit of inclisiran for major adverse cardiovascular (MACE) events in participants with established cardiovascular disease (CVD) | From randomization to 72 months, the time of first occurrence of 3P-MACE (death from cardiovascular events, non-fatal myocardial infarction, and non-fatal ischemic stroke) | 2021-11-23 to 2027-10-13 | Underway |
| ORION-4 | Patients with confirmed ASCVD | Participants were randomized 1: 1 | A randomized, double-blind, placebo-controlled trial | To evaluate the effect of inclisiran on major adverse cardiovascular events in patients with confirmed ASCVD | Number of participants who experienced a major adverse cardiovascular event (MACE) | 2018-10-30 to 2026-07-30 | Underway |
| V-DIFFERENCE | Individually optimized lipid-lowering therapy for patients with hypercholesterolemia | Participants were randomized 1: 1 | A randomized, double-blind, placebo-controlled, multicenter phase V trial | To evaluate the efficacy, safety, tolerability, and quality of life of inclisiran in patients with continuous individual-optimized lipid-lowering therapy | Percentage of participants who met their personal LDL-C control goal (<55 mg/dL or <70 mg/dL) at day 90 | 2022-04-08 to 2025-03-26 | Underway |
| Study name | Study object | Study group | Study design | Study target | Primary outcome measures | Research time | Study status |
| VICTORION-2P | Patients with confirmed cardiovascular disease (CVD) | Participants were randomized 1: 1 | A randomized, double-blind, placebo-controlled, multicenter trial | To evaluate the benefit of inclisiran for major adverse cardiovascular (MACE) events in participants with established cardiovascular disease (CVD) | From randomization to 72 months, the time of first occurrence of 3P-MACE (death from cardiovascular events, non-fatal myocardial infarction, and non-fatal ischemic stroke) | 2021-11-23 to 2027-10-13 | Underway |
| ORION-10 | Patients with ASCVD with elevated LDL-C | Participants were randomized 1: 1 | A randomized, double-blind, placebo-controlled, phase III trial | To evaluate the efficacy, safety, and tolerability of subcutaneous injections of inclisiran | Percentage change in LDL-C levels from baseline to day 510 | 2017-12-21 to 2019-09-17 | Completed |
| ORION-6 | Patients with liver impairment | According to the Child-Pugh grade, the patients were divided into normal, mild and moderate liver injury groups | A single-dose, open-label, parallel-group, phase I trial | To evaluate the pharmacokinetics, pharmacodynamics, and safety of inclisiran in patients with mild or moderate hepatic impairment vs participants with normal hepatic function | Pharmacokinetic indices at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 144 h after administration and at day 14 and day 30 after administration | 2018-11 to 2019-05 | Completed |